Faculty Bibliography

Contrast processing is a fundamental function of the visual system, and contrast sensitivity as a function of spatial frequency (CSF) provides critical information about the integrity of the system. Here, we used a novel iPad-based instrument to collect CSFs and fitted the data with a difference of Gaussians model to investigate the neurophysiological bases of the spatial CSF. The reliability of repeat testing within and across sessions was evaluated in a sample of 22 adults for five spatial frequencies (0.41-13 cycles/degree) and two temporal durations (33 and 500 ms). Results demonstrate that the shape of the CSF, lowpass versus bandpass, depends on the temporal stimulus condition. Comparisons with previous psychophysical studies and with single-cell data from macaques and humans indicate that the major portion of the CSF, spatial frequencies >1.5 cycles/degree regardless of temporal condition, is determined by a 'sustained' mechanism (presumably parvocellular input to primary visual cortex [V1]). Contrast sensitivity to the lowest spatial frequency tested appears to be generated by a 'transient' mechanism (presumably magnocellular input to V1). The model fits support the hypothesis that the high spatial frequency limb of the CSF reflects the receptive field profile of the center mechanism of the smallest cells in the parvocellular pathway. These findings enhance the value of contrast sensitivity testing in general and increase the accessibility of this technique for use by clinicians through implementation on a commercially-available device.

PURPOSE/OBJECTIVE:Frequency-domain measures were applied to characterize neural deficits in individuals with schizophrenia using transient visual evoked potentials (tVEP). These measures were compared with conventional time-domain measures to elucidate underlying neurophysiological mechanisms and examine the value of frequency analysis. METHODS:Four frequency bands of activity identified in previous work were explored with respect to magnitude (spectral power), timing (phase), a combined measure, magnitude-squared coherence (MSC), and compared to amplitudes and times of prominent deflections in the response. RESULTS:Band 2 power/MSC (14-28 Hz) captured the major deflections in the waveform and its power predicted N75-P100 amplitude for patients and controls. Band 3 power/MSC (30-40 Hz) correlated highly with the earliest deflection (P60-N75), reflecting input to primary visual cortex (V1) and produced the largest magnitude effect. Phase of the 24th harmonic component predicted P100 peak time for patients and controls and yielded the largest group difference. Cluster analyses including time- and frequency-domain measures identified subgroups of patients with differential neurophysiological effects. A small but significant difference in visual acuity was found between groups that appears to be neurally based: Acuity (range 0.63-1.6) was not correlated with any tVEP measures in controls nor with input timing to V1 (P60 peak time) in patients, but was correlated with later tVEP measures in patients. All but two of the patients were on antipsychotic medication: Medication level (chlorpromazine equivalents) was correlated negatively with tVEP time measures and positively with certain magnitude measures yielding responses similar to controls at high levels. CONCLUSIONS:Overall, frequency-domain measures were shown to be objective and recommended as an alternative to conventional, subjective time-domain measures for analyzing tVEPs and in distinguishing between groups (patients vs. controls and patient subgroups). The findings implicated a loss of excitatory input to V1 in schizophrenia. Acuity as measured in the current study reflected disease status, and medication level was associated with improved tVEP responses. These novel tVEP techniques may be useful in revealing neurophysiological processes affected in schizophrenia and as a clinical tool.

Studies across a broad range of disciplines-from psychiatry to cognitive science to behavioral neuroscience-have reported on whether the magnitude of contrast sensitivity alterations in one group or condition varies with spatial frequency. Significant interactions have often gone unexplained or have been used to argue for impairments in specific processing streams. Here, we show that interactions with spatial frequency may need to be re-evaluated if the inherent skew/heteroscedasticity was not taken into account or if visual acuity could plausibly differ across groups or conditions. By re-analyzing a publicly available data set, we show that-when using raw contrast sensitivity data-schizophrenia patients exhibit an apparent contrast sensitivity impairment at low, but not high, spatial frequencies, but that when using log-transformed data or when using generalized estimating equations, this interaction reversed. The reversed interaction, but not the overall contrast sensitivity deficit, would disappear if groups were matched on visual acuity. An analysis of the contrast threshold data yielded similar results. A caveat is that matching groups on acuity is probably only defensible if acuity differences arise from non-neural factors such as optical blur. Taken together, these analyses reconcile seemingly discrepant findings in the literature and demonstrate that reporting contrast sensitivity interactions with spatial frequency requires properly accounting for visual acuity and skew/heteroscedasticity.

Previous studies have shown that patients diagnosed with schizophrenia (SCZ) have deficits in early visual processing, namely contrast processing. The brain-derived neurotropic factor (BDNF) is an important measure to investigate neuroplasticity in some visual functions like visual perception. In this study, we investigated the relationship between visual processing and BDNF levels in first-episode SCZ patients. Thirty-nine healthy controls and 43 first-episode SCZ patients were enrolled. Contrast sensitivity measurements were conducted using low, mid- and high spatial frequencies. First-episode SCZ patients had higher contrast sensitivity than healthy controls for all frequencies, except for the middle spatial frequency. Negative correlations were found between BDNF, contrast sensitivity and clinical variables, mostly for middle and high spatial frequencies among females. Our results provide support for (i) the association of SCZ with alterations of magno- and parvocellular pathway functioning and (ii) decreased BDNF levels in first-episode SCZ patients. This study highlights the importance of using biomarkers along with other measures to investigate visual processing in SCZ and other disorders.

BACKGROUND:Individuals with schizophrenia exhibit deficits in visual contrast processing, though less is known about how these deficits impact neurocognition and functional outcomes. This study investigated effects of contrast sensitivity (CS) on cognition and capacity for independent living in schizophrenia. METHODS:Participants were 58 patients with schizophrenia (n = 49) and schizoaffective disorder (n = 9). Patients completed a psychophysical paradigm to obtain CS with stimuli consisting of grating patterns of low (0.5 and 1 cycles/degree) and high spatial frequencies (4, 7, 21 cycles/degree). Patients completed the MATRICS Consensus Cognitive Battery and Wechsler Adult Intelligence Scales, Third Edition to assess cognition, and the problem-solving factor of the Independent Living Scales to assess functional capacity. We computed bivariate correlation coefficients for all pairs of variables and tested mediation models with CS to low (CS-LSF) and high spatial frequencies (CS-HSF) as predictors, cognitive measures as mediators, and capacity for independent living as an outcome. RESULTS:Cognition mediated the relationship between CS and independent living with CS-LSF a stronger predictor than CS-HSF. Mediation effects were strongest for perceptual organization and memory-related domains. In an expanded moderated mediation model, CS-HSF was found to be a significant predictor of independent living through perceptual organization as a mediator and CS-LSF as a moderator of this relationship. CONCLUSION/CONCLUSIONS:CS relates to functional capacity in schizophrenia through neurocognition. These relationships may inform novel visual remediation interventions.

Individuals with schizophrenia have problems with visual contrast processing. The current study investigated contrast sensitivity (CS) in schizophrenia/schizoaffective disorder to elucidate the underlying neural mechanisms affected by this disorder and to identify critical testing conditions that distinguish individuals with the disorder from healthy individuals. Principal component analysis was applied to the data (N = 143) to separate responses from distinct visual pathways. Participants were 68 patients and 75 age-similar controls. CS was obtained using a forced-choice psychophysical paradigm with grating patterns of low to high spatial frequency presented at short and long durations. Linear mixed-effects models were used to examine differences in log CS with respect to group, duration, and stimulus condition. Lower CSs were found in patients compared to controls over all stimulus conditions with the magnitude of deficits dependent on both spatial frequency and stimulus duration. Log CSs to low and high spatial frequencies loaded onto separate principal components, supporting the existence of two psychophysical mechanisms, transient and sustained. Critical conditions were identified to tap each mechanism. Visual acuity was correlated moderately with log CS to high, but not low, spatial frequencies, and deficits found for acuity and CS to moderate/high spatial frequencies (4-21 cycles/degree) appear to reflect dysfunction in the sustained mechanism. CS deficits found at the lowest spatial frequency tested (0.5 cycles/degree) appear to reflect dysfunction in the transient mechanism. Both types of CS deficits may have diagnostic value and implications for social and neurocognitive deficits in this disorder.

Schizophrenia (Sz) is associated with deficits in fluent reading ability that compromise functional outcomes. Here, we utilize a combined eye-tracking, neurophysiological, and computational modeling approach to analyze underlying visual and oculomotor processes. Subjects included 26 Sz patients (SzP) and 26 healthy controls. Eye-tracking and electroencephalography data were acquired continuously during the reading of passages from the Gray Oral Reading Tests reading battery, permitting between-group evaluation of both oculomotor activity and fixation-related potentials (FRP). Schizophrenia patients showed a marked increase in time required per word (d = 1.3, P < .0001), reflecting both a moderate increase in fixation duration (d = .7, P = .026) and a large increase in the total saccade number (d = 1.6, P < .0001). Simulation models that incorporated alterations in both lower-level visual and oculomotor function as well as higher-level lexical processing performed better than models that assumed either deficit-type alone. In neurophysiological analyses, amplitude of the fixation-related P1 potential (P1f) was significantly reduced in SzP (d = .66, P = .013), reflecting reduced phase reset of ongoing theta-alpha band activity (d = .74, P = .019). In turn, P1f deficits significantly predicted increased saccade number both across groups (P = .017) and within SzP alone (P = .042). Computational and neurophysiological methods provide increasingly important approaches for investigating sensory contributions to impaired cognition during naturalistic processing in Sz. Here, we demonstrate deficits in reading rate that reflect both sensory/oculomotor- and semantic-level impairments and that manifest, respectively, as alterations in saccade number and fixation duration. Impaired P1f generation reflects impaired fixation-related reset of ongoing brain rhythms and suggests inefficient information processing within the early visual system as a basis for oculomotor dyscontrol during fluent reading in Sz.

Face recognition is an essential activity of social living, common to many primate species. Underlying processes in the brain have been investigated using various techniques and compared between species. Functional imaging studies have shown face-selective cortical regions and their degree of correspondence across species. However, the temporal dynamics of face processing, particularly processing speed, are likely different between them. Across sensory modalities activation of primary sensory cortices in macaque monkeys occurs at about 3/5 the latency of corresponding activation in humans, though this human simian difference may diminish or disappear in higher cortical regions. We recorded scalp event-related potentials (ERPs) to presentation of faces in macaques and estimated the peak latency of ERP components. Comparisons of latencies between macaques (112 ms) and humans (192 ms) suggested that the 3:5 ratio could be preserved in higher cognitive regions of face processing between those species.

BACKGROUND:Optical coherence tomography (OCT) studies have demonstrated differences between people with schizophrenia and controls. Many questions remain including the agreement between scanners. The current study seeks to determine inter-device agreement of OCT data in schizophrenia compared to controls and to explore the relations between OCT and visual function measures. METHODS:Participants in this pilot study were 12 individuals with schizophrenia spectrum disorders and 12 age- and sex-matched controls. Spectralis and Cirrus OCT machines were used to obtain retinal nerve fiber layer (RNFL) thickness and macular volume. Cirrus was used to obtain ganglion cell layer + inner plexiform layer (GCL + IPL) thickness. Visual function was assessed with low-contrast visual acuity and the King-Devick test of rapid number naming. RESULTS:There was excellent relative agreement in OCT measurements between the two machines, but poor absolute agreement, for both patients and controls. On both machines, people with schizophrenia showed decreased macular volume but no difference in RNFL thickness compared to controls. No between-group difference in GCL + IPL thickness was found on Cirrus. Controls showed significant associations between King-Devick performance and RNFL thickness and macular volume, and between low-contrast visual acuity and GCL + IPL thickness. Patients did not show significant associations between OCT measurements and visual function. CONCLUSIONS:Good relative agreement suggests that the offset between machines remains constant and should not affect comparisons between groups. Decreased macular volume in individuals with schizophrenia on both machines supports findings of prior studies and provides further evidence that similar results may be found irrespective of OCT device.

We report on the ongoing R21 project "Social Reward Learning in Schizophrenia". Impairments in social cognition are a hallmark of schizophrenia. However, little work has been done on social reward learning deficits in schizophrenia. The overall goal of the project is to assess social reward learning in schizophrenia. A probabilistic reward learning (PRL) task is being used in the MRI scanner to evaluate reward learning to negative and positive social feedback. Monetary reward learning is used as a comparison to assess specificity. Behavioral outcomes and brain areas, included those involved in reward, are assessed in patients with schizophrenia or schizoaffective disorder and controls. It is also critical to determine whether decreased expected value (EV) of social stimuli and/or reward prediction error (RPE) learning underlie social reward learning deficits to inform potential treatment pathways. Our central hypothesis is that the pattern of social learning deficits is an extension of a more general reward learning impairment in schizophrenia and that social reward learning deficits critically contribute to deficits in social motivation and pleasure. We hypothesize that people with schizophrenia will show impaired behavioral social reward learning compared to controls, as well as decreased ventromedial prefrontal cortex (vmPFC) EV signaling at time of choice and decreased striatal RPE signaling at time of outcome, with potentially greater impairment to positive than negative feedback. The grant is in its second year. It is hoped that this innovative approach may lead to novel and more targeted treatment approaches for social cognitive impairments, using cognitive remediation and/or brain stimulation.